Minimal Functional Sites in Metalloproteins and Their Usage in Structural Bioinformatics

Rosato, Antonio; Valasatava, Yana; Andreini, Claudia

doi:10.3390/ijms17050671

Cited by 13 publications

(15 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These included the C 2 H 2 -like zinc fingers and Zn 2 Cys 6 zinc fingers most often found in DNA-binding transcription factors (34). Additional structural zinc-binding motifs observed included zinc ribbons, treble clef motifs, and zinc necklace domains (35). Some proteins bind multiple zinc atoms and have more than one type of site.…”

Section: Resultsmentioning

confidence: 99%

“…The procedure resulted in a set of 573 Pfam domains: 541 with an associated zinc-containing 3D structure, and an additional 32 annotated as zinc-binding domains. The library of zinc-binding structural motifs was created by splitting into fragments the zinc-binding sites stored in MetalPDB as of June 2017, as described in Rosato et al (35). Only one representative was kept for zinc-binding sites that, though found in different PDB structures, fall in the same position of the same protein domain.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

The cellular economy of the Saccharomyces cerevisiae zinc proteome

et al. 2018

Self Cite

View full text Add to dashboard Cite

Zinc is an essential cofactor for many proteins. A key mechanism of zinc homeostasis during deficiency is “zinc sparing” in which specific zinc-binding proteins are repressed to reduce the cellular requirement. In this report, we evaluated zinc sparing across the zinc proteome of Saccharomyces cerevisiae. The yeast zinc proteome of 582 known or potential zinc-binding proteins was identified using a bioinformatics analysis that combined global domain searches with local motif searches. Protein abundance was determined by mass spectrometry. In zinc-replete cells, we detected over 2500 proteins among which 229 were zinc proteins. Based on copy number estimates and binding stoichiometries, a replete cell contains ~9 million zinc-binding sites on proteins. During zinc deficiency, many zinc proteins decreased in abundance and the zinc-binding requirement decreased to ~5 million zinc atoms per cell. Many of these effects were due at least in part to changes in mRNA levels rather than simply protein degradation. Measurements of cellular zinc content showed that the level of zinc atoms per cell dropped from over 20 million in replete cells to only 1.7 million in deficient cells. These results confirmed the ability of replete cells to store excess zinc and suggested that the majority of zinc-binding sites on proteins in deficient cells are either unmetalated or mismetalated. Our analysis of two abundant zinc proteins, Fba1 aldolase and Met6 methionine synthetase, supported that hypothesis. Thus, we have discovered widespread zinc sparing mechanisms and obtained evidence of a high accumulation of zinc proteins that lack their cofactor during deficiency.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

The cellular economy of the Saccharomyces cerevisiae zinc proteome

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…MetalPDB ( 4 ) is a resource derived from the automated analysis of all the three-dimensional (3D) structures of the adducts between biological macromolecules and metal ions or metal-containing cofactors available from the Protein Data Bank (PDB, http://www.wwpdb.org/ ) ( 5 ). MetalPDB stores the metal sites observed in PDB structures in the form of Minimal Functional Sites (MFSs) ( 6 ; 7 ). Each MFS is the ensemble of atoms of the metal cofactor, the metal ligands and any other residue or chemical species within 5 Å from a ligand.…”

Section: Introductionmentioning

confidence: 99%

MetalPDB in 2018: a database of metal sites in biological macromolecular structures

Putignano

Rosato

Banci

et al. 2017

Nucleic Acids Research

Self Cite

178

164

View full text Add to dashboard Cite

MetalPDB (http://metalweb.cerm.unifi.it/) is a database providing information on metal-binding sites detected in the three-dimensional (3D) structures of biological macromolecules. MetalPDB represents such sites as 3D templates, called Minimal Functional Sites (MFSs), which describe the local environment around the metal(s) independently of the larger context of the macromolecular structure. The 2018 update of MetalPDB includes new contents and tools. A major extension is the inclusion of proteins whose structures do not contain metal ions although their sequences potentially contain a known MFS. In addition, MetalPDB now provides extensive statistical analyses addressing several aspects of general metal usage within the PDB, across protein families and in catalysis. Users can also query MetalPDB to extract statistical information on structural aspects associated with individual metals, such as preferred coordination geometries or aminoacidic environment. A further major improvement is the functional annotation of MFSs; the annotation is manually performed via a password-protected annotator interface. At present, ∼50% of all MFSs have such a functional annotation. Other noteworthy improvements are bulk query functionality, through the upload of a list of PDB identifiers, and ftp access to MetalPDB contents, allowing users to carry out in-depth analyses on their own computational infrastructure.

show abstract

“…Recently, Rosato et al proposed the concept of minimal functional sites in order to describe structure-function relations in metalloproteins [ 34 ]. Minimal functional sites were defined as 3D structures with conserved geometry that include the nearby region around the metal site and did not depend on the macromolecular structure of the protein.…”

Section: Discussionmentioning

confidence: 99%

XANES Measurements for Studies of Adsorbed Protein Layers at Liquid Interfaces

et al. 2020

View full text Add to dashboard Cite

X-ray absorption near edge structure (XANES) spectra for protein layers adsorbed at liquid interfaces in a Langmuir trough have been recorded for the first time. We studied the parkin protein (so-called E3 ubiquitin ligase), which plays an important role in pathogenesis of Parkinson disease. Parkin contains eight Zn binding sites, consisting of cysteine and histidine residues in a tetracoordinated geometry. Zn K-edge XANES spectra were collected in the following two series: under mild radiation condition of measurements (short exposition time) and with high X-ray radiation load. XANES fingerprint analysis was applied to obtain information on ligand environments around zinc ions. Two types of zinc coordination geometry were identified depending on X-ray radiation load. We found that, under mild conditions, local zinc environment in our parkin preparations was very similar to that identified in hemoglobin, treated with a solution of ZnCl2 salt. Under high X-ray radiation load, considerable changes in the zinc site structure were observed; local zinc environment appeared to be almost identical to that defined in Zn-containing enzyme alkaline phosphatase. The formation of a similar metal site in unrelated protein molecules, observed in our experiments, highlights the significance of metal binding templates as essential structural modules in protein macromolecules.

show abstract

Minimal Functional Sites in Metalloproteins and Their Usage in Structural Bioinformatics

Cited by 13 publications

References 61 publications

The cellular economy of the Saccharomyces cerevisiae zinc proteome

The cellular economy of the Saccharomyces cerevisiae zinc proteome

MetalPDB in 2018: a database of metal sites in biological macromolecular structures

XANES Measurements for Studies of Adsorbed Protein Layers at Liquid Interfaces

Contact Info

Product

Resources

About